Vitamin K Supplementation in Post-Menopausal Osteopenia

Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia (ECKO Trial)

The purpose of this study is to determine whether supplementation with 5 mg vitamin K daily over a 2-year period will prevent bone loss in post-menopausal women with osteopenia.

Study Overview

• Status: Completed
• Conditions: Post-Menopausal Osteoporosis; Post-Menopausal Osteopenia
• Intervention / Treatment: Dietary supplement: vitamin K1 (phylloquinone); Dietary supplement: placebo

Detailed Description

Osteoporosis is major cause of morbidity and mortality in Canadian postmenopausal women. It is a systemic disease characterized by low bone mass and deterioration of bone microarchitecture, resulting in bone fragility and an increased risk of fractures. One in six women over the age of 50 have osteoporosis. The lifetime risk of an osteoporotic fracture for an average 50 year-old Canadian woman is >40%. The annual health care costs for osteoporotic fractures in Canada have been estimated to exceed $1.3 billion.

Recent data suggest that vitamin K supplements may decrease bone loss and prevent fractures. Vitamin K is a co-factor of gamma-glutamyl carboxylase, an enzyme that catalyzes the gamma-carboxylation of glutamic acid residues in bone matrix proteins such as osteocalcin. Vitamin K has been reported to enhance bone formation in both in vitro studies and in vivo studies in animals. Vitamin K levels are low in individuals with osteoporosis and in patients with osteoporotic fractures. The few studies examining vitamin K supplementation in humans have showed promising results with no significant side effects, but these studies had significant methodological shortcomings such as inadequate sample size and lack of randomization.

The primary objective of our study is to examine whether vitamin K supplementation will increase bone mineral density in postmenopausal women with osteopenia. Our secondary objectives are to examine the possible adverse effects from long-term vitamin K supplementation, to investigate whether vitamin K will decrease risk of fractures and to determine if vitamin K affects quality of life. Our hypotheses are that vitamin K increases bone mineral density in postmenopausal women, and that there are no significant adverse effects from vitamin K supplementation.

• Study Type: Interventional
• Enrollment (Actual): 440
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 3E2
      • University of Toronto
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network, Osteoporosis Department
    • Toronto, Ontario, Canada, M5G 1X5
      • Mt. Sinai Hospital
    • Toronto, Ontario, Canada, M5S 1B2
      • Sunnybrook & Women's College Health Sciences Centre
    • Toronto, Ontario, Canada, M5C 2T2
      • St. Michael's Hospital Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Postmenopausal: One year since the natural cessation of menses, or Hysterectomy with either postmenopausal status confirmed by FSH lab values, or age 55 and above AND 2. Osteopenic: T-score at baseline has to be between (and including) -1.0 and

-2.0 in the lumbar spine (L1-L4), total hip or femoral neck, and the lowest reading of the above three measurements must be between -1.0 and -2.0

Exclusion Criteria:

1. Women ever having had a fragility fracture after age 40;
2. Women currently on anticoagulants, previously on anticoagulants in the past 3 months, or expected to be on anticoagulants in the near future;
3. Women on hormone replacement therapy, raloxifene, bisphosphonates or calcitonin during the past 3 months;
4. Women who have ever been on a bisphosphonate for more than 6 months;
5. Women previously diagnosed with Paget's disease, hyperparathyroidism, hyperthyroidism or other metabolic bone diseases;
6. Women with decompensated diseases of the liver, kidney, pancreas, lung, or heart;
7. Women with a history of active cancer in the past 5 years;
8. Women taking mega-doses of vitamin A (more than 10,000 iu per day) or E (more than 400 iu per day);
9. Women involved in other clinical trials;
10. Any women who, in the opinion of the principal investigator, is at poor medical or psychiatric risk for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Dietary supplement: placebo; 1 pill daily
Experimental: phyloquinone; 5 mg Vitamin K1	Dietary supplement: vitamin K1 (phylloquinone)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer	0 to 24 months
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer	0 to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer	0 to 24 months
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer	0 to 24 months
Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker	measured by osteocalcin on elecsys platform	0-24 months
Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX)	measured by CTX Elisa assay on elecsys platform	0-24 months
Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin	measured by osteocalcin hydroxyapatite binding assay	0 to 24 months
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer	0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer	0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer	0 to 48 months
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.	BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer	0 to 48 months
Difference in Serious Adverse Events	These include hospitalizations for pneumonia, heart failure, gastro-intestinal bleeding, elective and non-elective surgery, cancer and death.	up to 48 months
Difference in Number of New Cancers by Treatment Arm.		up to 48 months
Difference in Number of New Clinical Fractures by Treatment Arm.	these included fragility fractures	up to 48 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Angela M Cheung, MD, PhD, University Health Network, University of Toronto

Publications and helpful links

General Publications

• Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008 Oct 14;5(10):e196. doi: 10.1371/journal.pmed.0050196. Erratum In: PLoS Med. 2008 Dec;5(12):e247.

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: September 6, 2005
• First Submitted That Met QC Criteria: September 6, 2005
• First Posted (Estimated): September 8, 2005

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: osteoporosis; women's health; bone mineral density; post-menopausal women; vitamin K; randomized double blind placebo controlled trial
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K; Vitamin K 1
• Other Study ID Numbers: 01-0169; 50422 (Other Grant/Funding Number: Canadian Institute for Health Research (CIHR))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No